In U.S. Pat. No. 4,446,113, there is disclosed 6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidinyl)-2H-1-benzo pyran 3-ol (BRL-34915). In European Patent Publication No. 273,262, British Patent Publication No. 2,204,868 and European Patent Publication No. 296,975, there are disclosed a group of 4-substituted benzopyran compounds having antihypertensive actions, smooth muscle-relaxant actions and the like.
Moreover, in European Patent Publication No. 339,562, there is disclosed that the novel benzopyran compounds bearing a N-acyl-N-oxy-substituted amino group or hydrazine group at the 4-position, possess hypotensive, coronary blood flow-increasing activities and the like.
Recently, in developing a compound having a chiral carbon atom(s) as drugs, the corresponding optical isomer has become important from the view point of enhancement of the pharmacological activity, removal of the side effect or improvement of the solubility and the like.
The optically active benzopyran compounds having hypotensive or coronary blood flow-increasing activities and the like are disclosed in, for example, European Patent Publication No. 120,428, British Patent Publication No. 2,204,868 and European Patent Publication No. 339,562.
In particular, in British Patent Publication No. 2,204,868, it is disclosed that optically active 3,4-dihydro-3,4-epoxy-2H-1-benzopyran compounds can be obtained by reacting trans-3-bromo-2,2-dimethyl-4-hydroxy-2H-1-benzopyran-6-carbonitrile with (-)-camphanic acid, subjecting the mixture of the obtained diastereomers to silica gel chromatography and then subjecting each of diastereomers to hydrolysis. However, (-)-camphanic acid itself is very expensive, and further, the resolution operation of diastereomers by chromatography consumes a long period of time and a lot of solvents and carriers. In brief, such operation is expensive and complicated, and is not suitable for resolution on a large scale. Though, European Patent Publication No. 339,562 describes that the optically active benzopyran compounds can be produced by employing the optically active starting compounds, no working examples for such starting compounds are illustrated. Therefore, the development of a practically useful method for the resolution has been desired.